New preparation method of [<18>F]FBPA

Abstract

The invention discloses a new preparation method of [<18>F]FBPA. The preparation method comprises: synthesizing an aryl iodide compound containing a BPA core skeleton; synthesizing a standard compound; synthesizing a highly-valent iodine ylide-labeled precursor; and synthesizing [<18>F]FBPA by using the highly-valent iodine ylide-labeled precursor B through two methods of a manual labeling experiment operation process and an automated synthesis experiment operation process. According to the present invention, with the new preparation method of [<18>F]FBPA, the novel substrate precursor is designed, the new carrier-free radioactive fluorine-18 negative ion preparation method of [<18>F]FBPA is performed, and specifically the radiochemical reaction is performed by using various novel highly-valent iodine ylide precursors; the method has advantages of simple operation, high yield, good repeatability and automatic production; and the radiotracer [<18>F]FBPA synthesized by the method has advantages of high specific activity, high chemical purity and high radioactive purity, and meets the quality standards of positron drugs for injection.

Description

technical field [0001] The present invention relates to the field of PET positron tracers, specifically a kind of [ 18 F] FBPA novel preparation method. Background technique [0002] Boron Neutron Capture Therapy (BNCT) is a new type of binary targeted radiotherapy, which belongs to a biologically targeted radiotherapy mode with "inherent" safety. Nodular or metastatic tumors have the possibility of being cured. It destroys cancer cells through nuclear reactions in tumor cells, and is a technology that selectively kills cancer cells with complex shapes without damaging normal tissues. [0003] The principle of BNCT is to combine isotope-containing 10 The compound of B is injected into the human body, and the compound will be concentrated in tumor cells. This boron-containing compound is non-toxic and harmless to the human body, and has no therapeutic effect on cancer; After local neutron beam irradiation with thermal neutron rays, the tumor tissue 10 The B isotope under...

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Problems solved by technology

[0005] However, the above-mentioned standard course of treatment in developed countries has encountered great difficulties in the implementation process in China, mainly due to the use of PET tracers before and after treatment [ 18 F] FBPA does not have an efficient synthesis method to carry out clinical imaging studies

At present, for the synthesis of the tracer, there are three methods reported internationally, the first synthesis method adopts [ 18 F]F 2 (References: K. Ishiwata, T. Ido, et al. Appl. Radiat. Isot. 1991, 42 , 325-328), on the one hand the yield of this reaction is very low (18 F]F 2 The generating device has strong corrosiveness, and there is no corresponding supporting device in major hospitals and positron drug production institutions in China, so there is no application prospect in China

The total synthesis yield of the second synthesis method is generally about 25%, which is relatively high, but due to the long reaction route, it is difficult to automate the synthesis, and the above-mentioned conversion cannot be realized in most domestic positron drug production centers, so this method is also impossible. universal

However, due to the use of aryl boronate precursors in the first step of conversion (references: M. Tredwell, S. M. PreschLock, et al. Angew. .2014, 53 , 7751-7755), in the process of fluorination, it is necessary to add copper metal reagents and blow a certain amount of air. TM FX FN For the automation modules equipped in most domestic hospitals, including equipment, automatic conversion and synthesis are extremely challenging

On the other hand, due to the addition of copper metal reagents and air, it is required to perform a silica gel column chromatography purification after the first step of the reaction, which also brings difficulties to automatic conversion.

Therefore, this route also failed to effectively promote

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